Genetic contributions to rare childhood lung diseases

Epidemiological studies have suggested that many rare diseases with respiratory involvement have a genetic component. Molecular advances have increased the understanding of the pathophysiology of these diseases which has led to better diagnostic and prognostic methods. There may be many genes responsible for diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in addition to the effect of modifier genes. The genotype:phenotype correlation in these diseases remains to be elucidated. In some diseases, such as familial dysautonomia and sickle cell, the gene has been identified which allows for accurate pre-natal testing. Further, in diseases where the genetic abnormality is known, such as chronic granulomatous disease, gene therapy remains a realistic prospect and phase I studies are about to commence or currently underway. This article reviews those rare diseases in which there is or is likely to be a significant genetic contribution.